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Objective: To determine if the ages at pubertal milestones are associated with the prevalence of adolescent migraine. Background: Migraine headaches are a common disease in adolescent girls. Past studies have evaluated the relationship between age of onset of menarche and migraine headache, but none have studied earlier pubertal milestones such as thelarche and pubarche. Methods: In this cross-sectional study, a previously validated questionnaire was administered to girls (15–18 years) in Breast Cancer and the Environment Research Program puberty cohort to ascertain if they met criteria for migraine over the past year. Ages of pubertal development were ascertained by serial examinations beginning at 6–8 years of age and ending in late puberty. Logistic regression analyses determined if age of onset of each pubertal milestone (thelarche, pubarche, menarche separately) was associated with adolescent migraine after adjusting for other risk factors. Results: Of 761girls, 222 (29.2%) met the criteria for migraine. Later thelarche was associated with a lower odds of adolescent migraine (OR 0.83; 95% CI 0.72–0.97, p= 0.019). In models further adjusted for BASC-2 internalizing problems (n= 490), both later thelarche (OR 0.78; 95% CI 0.64–0.96, p= 0.016) and later menarche (OR 0.81; 95%CI 0.67–0.98, p= 0.026) were associated with a lower migraine prevalence. Internalizing problems (OR 1.05; 95% CI 1.03–1.07) externalizing problems (OR 1.05; 95% CI 1.02–1.07) and behavioral symptoms (OR 1.05; 95% CI 1.03–1.08) were associated with increased prevalence of migraine in separate models. Conclusions: Age of onset of thelarche and menarche, and internalizing, externalizing, and behavioral symptoms were all associated with adolescent migraine.

Background: Endometrial cancer is the most common female gynecologic cancer in the United States. Excessive and prolonged exposure of the endometrium to estrogens unopposed by progesterone and a high body mass are well-established risk factors for endometrial cancer. Although dietary fiber has been shown to beneficially reduce estrogen concentrations and prevent obesity, its role in endometrial cancer has received relatively little attention. Objective: The objective was to summarize and quantify the current evidence of a role of dietary fiber consumption in endometrial cancer risk and to identify research gaps in this field. Design: We conducted a systematic literature review of articles published through February 2007 to summarize the current evidence of a relation between dietary fiber consumption and endometrial cancer risk and to quantify the magnitude of the association by conducting a dose-response meta-analysis. Results: Ten articles representing 1 case-cohort study and 9 case-control studies that evaluated several aspects of fiber consumption and endometrial cancer risk were identified through searches in various databases. On the basis of 7 case-control studies, the random-effects summary risk estimate was 0.82 (95% CI: 0.75, 0.90) per 5 g/1000 kcal dietary fiber, with no evidence of heterogeneity ([I.sup.2]: 0%, P for heterogeneity: 0.55). The random-effects summary estimate was 0.71 (95% CI: 0.59, 0.85) for the comparison of the highest with the lowest dietary fiber intake in 8 case-control studies, with little evidence of heterogeneity ([I.sup.2]: 20.8%, P for heterogeneity: 0.26). In contrast, the only prospective study that evaluated this association did not find an association. Conclusions: Although the current evidence, based on data from case-control studies, supports an inverse association between dietary fiber and endometrial cancer, additional population-based studies, particularly cohort studies, are needed before definitive conclusions can be drawn. KEY WORDS Endometrial carcinoma, diet, fiber, meta-analysis, systematic literature review

BACKGROUND: A recent review of epidemiologic literature found consistently reduced cancer and heart disease rates in persons with high compared with low whole-grain intakes. Objective: We hypothesized that whole-grain intake was associated with a reduced risk of ischemic heart disease (IHD) death. Design: We studied 34492 postmenopausal women aged 55-69 y and free of IHD at baseline in 1986. There were 438 IHD deaths between baseline and 1995. Usual dietary intake was determined with use of a 127-item food-frequency questionnaire. Results: Whole-grain intake in median servings/d was 0.2, 0.9, 1.2, 1.9, and 3.2 for quintiles of intake. The unadjusted rate of IHD death was 2.0/1 x [10.sup.3] person-years in quintile 1 and was 1.7, 1.2, 1.0, and 1.4 IHD deaths/1 x [10.sup.3] person-years in succeeding quintiles (P for trend [is less than] 0.001). Adjusted for demographic, physiologic, behavioral, and dietary variables, relative hazards were 1.0, 0.96, 0.71, 0.64, and 0.70 in ascending quintiles (P for trend = 0.02). The lower risk with higher whole-grain intake was not explained by intake of fiber or several other constituents of whole grains. Conclusion: A clear inverse association between whole-grain intake and risk of IHD death existed. A causal association is plausible because whole-grain foods contain many phytochemicals, including fiber and antioxidants, that may reduce chronic disease risk. Whole-grain intake should be studied further for its potential to prevent IHD and cancer. Am J Clin Nutr 1998;68:248-57.

Background: The risks and benefits of hormone replacement therapy (HRT) are of considerable interest and importance, especially in terms of whether they differ among subsets of women. Objective: To determine whether HRT is associated with increased risks for breast cancer and total mortality in women with a family history of breast cancer. Design: Prospective cohort study. Setting: Population-based sample of midwestern post-menopausal women enrolled in an observational study of risk factors for cancer. Participants: Random sample of 41 837 female Iowa residents 55 to 69 years of age. Measurements: Incidence rates of and related risks for breast cancer (n = 1085) and total mortality (n = 2035) through 8 years of follow-up were calculated using data from the State Health Registry of Iowa and the National Death Index. Result: A family history of breast cancer was reported by 12.2% of the cohort at risk. Among women with a family history of breast cancer, those who currently used HRT and had done so for at least 5 years developed breast cancer at an age-adjusted annual rate of 61 cases per 10 000 person-years (95% Cl, 28 to 94 cases); this rate was not statistically significantly higher than the rate in women who had never used Hrt (46 cases per 10 000 person-years [Cl, 36 to 55 cases]). Among with a family history, those who used HRT had a significantly lower risk for total mortality than did women had never used HRT (relative risk, 0.67 [Cl. 0.51 to 0.89]), including total cancer-related mortality (relative risk, 0.75 [Cl, 0.50 to 1.12]). the age-adjusted annual mortality rate for women using HRT for at least 5 years was 46 deaths per 10 000 person-years (Cl, 19 to 74 deaths); this is roughly half the rate seen in women who had never used HRT (80 deaths per 10 000 person-years [Cl, 69 to 92 deaths]). Conclusion: These data suggest that HRT use in women with a family history of breast cancer is not associated with a significantly increased incidence of breast cancer but is associated with a significantly reduced total mortality rate., Women with a family history of breast cancer who take hormone replacement therapy (HRT) at menopause do not appear to be at increased risk for developing breast cancer and may actually be less likely to die of other causes. Rates of death, breast cancer, family history of breast cancer, and HRT use were analyzed among 41,837 midwestern women aged 55 to 69 years of age. Breast cancer rates were similar among women with a family history of breast cancer who either did or did not take HRT. Total death rates were nearly twice as high among women never taking HRT as those who had taken HRT for five years.

In epidemiologic studies, total energy intake is often related to disease risk because of associations between physical activity or body size and the probability of disease. In theory, differences in disease incidence may also be related to metabolic efficiency and therefore to total energy intake. Because intakes of most specific nutrients, particularly macronutrients, are correlated with total energy intake, they may be noncausally associated with disease as a result of confounding by total energy intake. In addition, extraneous variation in nutrient intake resulting from variation in total energy intake that is unrelated to disease risk may weaken associations. Furthermore, individuals or populations must alter their intake of specific nutrients primarily by altering the composition of their diets rather than by changing their total energy intake, unless physical activity or body weight are changed substantially. Thus, adjustment for total energy intake is usually appropriate in epidemiologic studies to control for confounding, reduce extraneous variation, and predict the effect of dietary interventions. Failure to account for total energy intake can obscure associations between nutrient intakes add disease risk or even reverse the direction of association. Several disease-risk models and formulations of these models are available to account for energy intake in epidemiologic analyses, including adjustment of nutrient intakes for total energy intake by regression analysis and addition of total energy to a model with the nutrient density (nutrient divided by energy).

Several carefully studied populations in Mediterranean countries and in some areas in Asia where traditional diets consisted largely of foods of plant origin exhibit low rates of many chronic diseases and long life expectancies. Many case-control and prospective studies have provided further evidence that high consumption of plant foods confers numerous health benefits. Investigations support links between increased vegetable, fruit, and fiber consumption,.and lower rates of several cancers, coronary heart disease (CHD), neural tube defects, and cataracts. Although the mechanisms are not fully understood, carotenoids, folic acid, and fiber, all abundant in the Mediterranean diet, appear to play important roles in prevention of these diseases. In contrast, much evidence suggests that high consumption of full-fat dairy products is likely to increase CHD risk. Epidemiologic studies have not provided evidence that high dairy product consumption by adults prevents fractures; in fact, the results of several studies suggest positive associations. Thus, the abundant fruit, vegetables, and whole grains, and the low to moderate intake of dairy products in traditional Mediterranean diets are likely to have contributed to the low rates of numerous chronic diseases observed in these populations.

Consumption of beef, pork, and lamb has traditionally been low in Mediterranean countries. Regular consumption of red meat has been associated in epidemiologic studies with increased risks of coronary heart disease (CHD) and colon and other cancers; possible mechanisms may involve dietary cholesterol, saturated fat, heme iron, and the presence of carcinogens formed in cooking. Also, high consumption of red meat, the major source of animal protein in most Western diets, increases urinary calcium losses and is therefore likely to contribute to osteoporotic fractures. In Mediterranean diets the major source of dietary fat has traditionally been olive oil, which, compared with saturated and partially hydrogenated fats, reduces low-density-lipoprotein (LDL) cholesterol and, compared with carbohydrates, increases high-density-lipoprotein (HDL) cholesterol. A wealth of epidemiologic evidence, supports a potent protective effect of moderate alcohol consumption against CHD, probably in part by increasing HDL concentrations. Although dietary factors alone may not fully explain the excellent health of Mediterranean populations, available evidence strongly suggests important contributions of high consumption of fruit, vegetables, and whole grains; moderate intake of alcohol; and low consumption of animal products, saturated and hydrogenated fats, and refined carbohydrates.

Background: Previous studies have suggested that cancers of the breast and prostate cluster in families and that the presence of both diseases in a family may be associated with increased risk of breast cancer. Purpose: Our purpose was to evaluate whether 1) prostate cancer aggregates in families with postmenopausal breast cancer, 2) families with cancers of the breast and prostate are the same ones as families with cancers of the breast and ovary, and 3) a family history of prostate cancer is associated with increased risk of postmenopausal breast cancer. Methods: We analyzed data from a large prospective cohort study of Iowa women that were (at baseline) aged 55-69 years in 1986. At the third follow-up survey in 1992, self-reported data on family history of breast, ovarian, and prostate cancers in parents and siblings were provided by 30 883 women. Additional information was collected to ascertain whether the age-of-onset of breast cancer in mothers or sisters was before or after the age of 45 years. Cancer occurrence was documented using the State Health Registry of Iowa. Results: History of prostate cancer in their father or a brother was reported by 3384 (11.0%) of the women, and a total of 4090 women (13.2%) reported breast cancer in their mother or a sister. A positive family history of both cancers was reported by 556 women, significantly (two-sided P

A controlled crossover feeding study was conducted in eight males aged 20--36 y to compare the effects of skim milk and whole milk on blood lipids. For 6-wk diet periods, 236 mL/4191 kJ of skim or whole milk was consumed with a background diet designed according to the American Heart Association recommendations. Plasma lipids were analyzed at baseline and at 3 and 6 wk. After 6 wk, the mean total cholesterol concentration was 4.47 mmol/L with skim milk and 4.80 mmol/L with whole milk (P [less than or equal to] 0.001); mean low-density-lipoprotein-cholesterol concentrations were 2.64 and 2.96 mmol/L, respectively (P [less than or equal to] 0.001). Mean apolipoprotein B decreased with skim milk and increased with whole milk (P [less than or equal to] 0.05). No statistically significant differences were observed for plasma high-density lipoprotein-cholesterol, triglyceride, apolipoprotein A-I, or fatty acids. Substitution of skim milk for whole milk may decrease the risk of coronary heart disease. Am J Clin Nutr 1994; 59:612--8.

It is increasingly common for analytic epidemiology studies of diet and disease to select a semi-quantitative food-frequency questionnaire for dietary assessment. Reasons include its low cost and focus on usual intake. However, the components of variation in nutrient intake based on such methods are poorly understood, and it does not provide a quantitative estimate of nutrient intakes. Because it is unlikely that such methods will be improved substantially, studies using a food-frequency questionnaire should include a dietary standardization substudy. A substudy, conducted in a sample of study participants and aimed at collecting multiple days of diet recall or record, provides data for quantitative calibration of frequency-derived nutrient intake estimates and adjustment of risk estimates for measurement error. Attention should also be directed at other aspects of study design, such as study population selection to maximize dietary exposure contrasts, that can increase the informativeness of epidemiologic studies.

Several studies have reported that vegetarians have a lower rate of heart disease and certain types of cancer than the general population. It has been recommended, therefore, that Americans eat less fat and more grains, vegetables, and fruits. However, the exact relationship between eating red meat and the risk of developing heart disease is not known. To investigate this issue, information regarding the daily dietary habits of 5,115 adults between the ages of 18 and 30 was obtained from a study called the Coronary Artery Risk Development in Young Adults (CARDIA) study. Only 2 percent of the subjects reported that they ate red meat or poultry less than once a week or not at all. These subjects consumed diets that were lower in fat and protein, and higher in carbohydrates, starch, fiber and vitamins than those who ate red meat on a regular basis. They were less likely to drink alcohol, had higher rates of physical activity, and had smaller body sizes than those who ate red meat and poultry more than once a week. Also, those who ate red meat and poultry more than once a week had higher blood levels of total cholesterol, low-density-lipoprotein (LDL) cholesterol and triglycerides (fatty acids) than those who ate red meat and poultry less frequently than once a week. (Consumer Summary produced by Reliance Medical Information, Inc.)

Many studies have reported that diets high in fat content increase both body weight and the risk of heart disease. High-fat diets lead to an increase in body weight because fat is high in calories, and high-fat diets tend to cause more calories to be taken in than are expended during daily activities. This causes adipose tissue to accumulate in the body. To further examine the relationship between dietary fat, energy intake and body weight, 303 women were studied. The women were between the ages of 45 and 69, and on average weighed between 145 and 152 pounds at the beginning of the study. Their average diet contained 39 percent of the total daily calories as fat. The women were divided into two groups that met on a regular basis. The first group (184 women) was taught how to replace fat in the diet with nonfatty or low-fat foods, while the 119 women in the second group continued their regular dietary habits. At the end of one year, the women who were taught how to select and substitute low-fat foods had reduced their daily fat intake by an average of 45 grams, reduced the fat content of their diets by 17 percent (from 39 percent to 22 percent), and lost an average of 6.8 pounds. The women in the second group only reduced the fat content of their diets by 2 percent and lost less than 1 pound. Reducing the fat content of the diet had a greater influence on reducing body weight than reducing the total amount of calories consumed. The results of this study indicate that body weight is related to energy balance and the fat content of the diet. (Consumer Summary produced by Reliance Medical Information, Inc.)

The Mediterranean diet is a well-studied cultural model of healthy eating, yet research on healthy models from other cultures and cuisines has been limited. This perspective article summarizes the components of traditional Latin American, Asian, and African Heritage diets, their association with diet quality and markers of health, and implications for nutrition programs and policy. Though these diets differ in specific foods and flavors, we present a common thread that emphasizes healthful plant foods, and that is consistent with high dietary quality and low rates of major causes of disability and deaths. In this perspective, we propose that nutrition interventions that incorporate these cultural models of healthy eating show promise, though further research is needed to determine health outcomes and best practices for implementation.

As next-generation sequencing(NGS) technology has become widely used to identify genetic causal variants for various diseases and traits, a number of packages for checking NGS data quality have sprung up in public domains. In addition to the quality of sequencing data, sample quality issues, such as gender mismatch, abnormal inbreeding coefficient, cryptic relatedness, and population outliers, can also have fundamental impact on downstream analysis. However, there is a lack of tools specialized in identifying problematic samples from NGS data, often due to the limitation of sample size and variant counts. We developed SeqSQC, a Bioconductorpackage, to automate and accelerate sample cleaning in NGS data of any scale. SeqSQCis designed for efficient data storage and access, and equipped with interactive plots for intuitive data visualization to expedite the identification of problematic samples. SeqSQCis available at http://bioconductor.org/packages/SeqSQC.

KATIE A. MEYER [1] LAWRENCE H. KUSHI [2] DAVID R. JACOBS [3] AARON R. FOLSOM [3] OBJECTIVE -- To examine the associations between reported intakes of dietary fat and incident [...]

Background: Antioxidant vitamins may play a role in the prevention of stroke because they scavenge free radicals and prevent LDL oxidation. Epidemiologic studies that have examined this relation produced conflicting results. Objective: We examined the association between antioxidant vitamin intakes and death from stroke. Design: This was a prospective cohort study of 34 492 postmenopausal women. Results: During follow-up, 215 deaths from stroke were documented. Total vitamin A, carotenoid, and vitamin E intakes were not associated with death from stroke after multivariate adjustment. Relative risks (RRs) and 95% CIs of the highest compared with the lowest category were 0.79 (0.45, 1.38; P for trend = 0.33) for vitamin A, 0.80 (0.45, 1.40; P for trend = 0.40) for carotenoids, and 0.91 (0.55, 1.52; P for trend = 0.86) for vitamin E. The test for trend for total vitamin C intake was significant, although the association appeared somewhat U-shaped, not monotonic. An inverse association was seen between death from stroke and vitamin E intake from food. RRs (and 95% CIs) of death from stroke from the lowest to highest intake categories were 1.0, 0.80 (0.51, 1.26), 0.93 (0.58, 1.49), 0.67 (0.39, 1.14), 0.40 (0.20, 0.80); P for trend = 0.008. The results suggest inverse associations between death from stroke and intakes of the most concentrated vitamin E food sources consumed by this cohort: mayonnaise, nuts, and margarine. Conclusions: Our results suggest a protective effect of vitamin E from foods on death from stroke but do not support a protective role for supplemental vitamin E or other antioxidant vitamins. However, given the number of deaths from stroke in the present cohort, a small-to-moderate association could not be ruled out. Am J Clin Nutr 2000;72:476-83. KEY WORDS Antioxidant vitamins, stroke, diet, postmenopausal women, food-frequency questionnaire, prospective cohort study, cardiovascular disease, Iowa Women's Health Study

Backgrounds Recent clinical guidelines on the health risks of obesity use body mass index (BMI; calculated as weight in kilograms divided by the square of height in meters) and waist circumference, but the waist-hip ratio may provide independent information. Methods: To assess the joint and relative associations of BMI, waist circumference, and waist-hip ratio with multiple disease end points, we conducted a prospective cohort study of 31702 Iowa women, aged 55 to 69 years and free of cancer, heart disease, and diabetes, assembled by random sampling and mail survey in 1986. Study end points were total and cause-specific mortality and incidence of site-specific cancers and self-reported diabetes, hypertension, and hip fracture over 11 to 12 years. Results: The waist-hip ratio was the best anthropometric predictor of total mortality, with the multivariable-adjusted relative risk for quintile 5 vs 1 of 1.2 (95% confidence interval, 1.1-1.4), compared with 0.91 (95% confidence interval, 0.8-1.0) for BMI and 1.1 (95% confidence interval, 1.0-1.3) for waist circumference. The waist-hip ratio was also associated positively with mortality from coronary heart disease, other cardiovascular diseases, cancer, and other causes. The waist-hip ratio was associated less consistently than BMI or waist circumference with cancer incidence. All anthropometric indexes were associated with incidence of diabetes and hypertension. For example, women simultaneously in the highest quintiles of BMI and waist-hip ratio had a relative risk of diabetes of 29 (95% confidence interval, 18-46) vs women in the lowest combined quintiles. Conclusion: The waist-hip ratio offers additional prognostic information beyond BMI and waist circumference. Arch Intern Med. 2000;160:2117-2128

Background: Dietary carbohydrates may influence the development of type 2 (non-insulin-dependent) diabetes, for example, through effects on blood glucose and insulin concentrations. Objective: We examined the relations of baseline intake of carbohydrates, dietary fiber, dietary magnesium, and carbohydraterich foods and the glycemic index with incidence of diabetes. Design: This was a prospective cohort study of 35988 older Iowa women initially free of diabetes. During 6 y of follow-up, 1141 incident cases of diabetes were reported. Results: Total grain, whole-grain, total dietary fiber, cereal fiber, and dietary magnesium intakes showed strong inverse associations with incidence of diabetes after adjustment for potential nondietary confounding variables. Multivariate-adjusted relative risks of diabetes were 1.0, 0.99, 0.98, 0.92, and 0.79 (P for trend: 0.0089) across quintiles of whole-grain intake; 1.0, 1.09, 1.00, 0.94, and 0.78 (P for trend: 0.005) across quintiles of total dietary fiber intake; and 1.0, 0.81, 0.82, 0.81, and 0.67 (P for trend: 0.0003) across quintiles of dietary magnesium intake. Intakes of total carbohydrates, refined grains, fruit and vegetables, and soluble fiber and the glycemic index were unrelated to diabetes risk. Conclusion: These data support a protective role for grains (particularly whole grains), cereal fiber, and dietary magnesium in the development of diabetes in older women. Am J Clin Nutr 2000;71:921-30. KEY WORDS Type 2 diabetes, non-insulin-dependent diabetes mellitus, diet, nutrition, prospective studies, carbohydrates, dietary fiber, sugar, glycemic index, grains, magnesium, Iowa Women's Health Study, women

Background: Intrauterine exposure to high levels of endogenous estrogens has been hypothesized to increase the risk of breast cancer. Because estrogens and other pregnancy hormones are substantially elevated in twin pregnancies, and possibly more so in dizygotic twin pregnancies, we evaluated the association between aspects of twin membership (i.e., belonging to a twin pair) and the risk of breast cancer. Methods: In a cohort of 29197 postmenopausal Iowa women with no prior diagnosis of cancer (except for nonmelanoma skin cancer), breast cancer risk factors were determined by use of a mailed questionnaire in 1986 (baseline); twin membership, sex of the twin, and zygosity were determined by use of a follow-up questionnaire in 1992. Results: Within the cohort, 1.8% (n = 538) of the women reported being a twin; of these, 24% (n = 130) were monozygotic twins, 63% (n = 337) were dizygotic twins, and 13% (n = 71) did not know their zygosity. From 1986 through 1996, 1230 breast cancers in the cohort were ascertained by linkage to the Iowa Cancer Registry. Compared with singletons, women who belonged to a twin pair were at elevated risk of breast cancer (multivariate-adjusted risk ratio [RR] = 1.72; 95% confidence interval [CI] = 1.22-2.42), with adjustment for educational level, family history of breast cancer, height, body mass index, body fat distribution, age at menarche, age at first live birth, use of hormone replacement therapy, and alcohol use. Multivariate-adjusted risk was elevated (in comparison with singletons) if the sex of the other twin was female (RR = 1.82; 95% CI = 1.20-2.75); however, this risk was limited to female dizygotic twins (RR = 2.14; 95% CI = 1.21-3.79), since no excess risk was evident for monozygotic twins (RR = 1.04; 95% CI = 0.43-2.50). The risk to women with a male twin was also elevated (RR = 1.49; 95% CI = 0.80-2.78) in comparison with singletons, but this estimate was not statistically significant. Conclusions: This cohort study lends further support to the theory that there are important intrauterine influences on carcinogenesis of the breast. [J Natl Cancer Inst 2000;92:261-5]

There is growing evidence that cereals and legumes play important roles in the prevention of chronic diseases. Early epidemiologic studies of these associations focused on intake of dietary fiber rather than intake of grains or legumes. Generally, these studies indicated an inverse association between dietary fiber intake and risk of coronary artery disease; this observation has been replicated in recent cohort studies. Studies that focused on grain or cereal intake are fewer in number; these tend to support an inverse association between intake of whole grains and coronary artery disease. Studies on the association of dietary fiber with colon and other cancers have generally shown inverse relations, but whether these relations are attributable to cereals, other fiber sources, or other factors; is less clear. Although legumes have been shown to lower blood cholesterol concentrations, epidemiologic studies are few and inconclusive regarding the association of legumes with risk of coronary artery disease. It has been hypothesized that legumes, in particular soybeans, reduce the risk of some cancers, but epidemiologic studies are equivocal in this regard. Overall, there is substantial epidemiologic evidence that dietary fiber and whole grains are associated with decreased risk of coronary artery disease and some cancers, whereas the role of legumes in these diseases appears promising but as yet inconclusive. Am J Clin Nutr 1999;70(suppl):451S-8S. KEY WORDS Dietary fiber, whole grains, legumes, cereals, coronary artery disease, cardiovascular disease, cancer, chronic disease risk, chronic disease prevention

The role of nutritional epidemiology studies in the development of nutritional recommendations has been controversial, in part because individual studies supporting either side of a given issue can often be identified. Several sets of criteria for inference of a causal relation between a dietary factor and a disease from epidemiologic studies have been suggested. One such set is that of Sir Austin Bradford Hill, which includes criteria such as strength of association, dose-response relation, consistency of association, temporally correct association, specificity of association, and biological plausibility. Another set of criteria, used by the US Preventive Services Task Force, ranks evidence according to study design, designating evidence from randomized controlled trials as superior to evidence from cohort or case-control studies, which are in turn superior to evidence from ecologic studies or opinions of respected authorities. The application of these criteria to the question of whether vitamin E intake is associated with coronary heart disease is examined here. It is suggested that the epidemiologic evidence from prospective cohort studies generally supports an inverse association of vitamin E intake and risk of coronary heart disease. The information available from randomized trials is limited but suggestive of an inverse association with nonfatal, but not with fatal, coronary events. It is suggested that the application of criteria for causal inference to specific questions in nutritional epidemiology may provide clarity to seemingly contradictory information. Am J Clin Nutr 1999;69(suppl): 1322S-9S.

Negative screening mammographic examinations were analyzed with five artificial intelligence (AI) algorithms; all predicted breast cancer risk to 5 years better than the Breast Cancer Surveillance Consortium (BCSC) clinical risk model and combining AI and BCSC models further improved prediction.

Supplemental Digital Content is available in the text.

BackgroundDietary phytoestrogens may alter hormonal activity in childhood. Flavonols and lignans are the most prevalent phytoestrogens in the Western diet. We examined whether higher intake of flavonols and lignans was associated with later age at menarche in a prospective study of young girls.MethodsIn all, 1,044 girls aged 6–8 years (mean 7.3 years) with two to four 24-h dietary recalls during their baseline year were followed up for 11 years until the attainment of menarche in the Breast Cancer and Environment Research Project (BCERP). Associations of age at menarche with quintiles of phytoestrogens were assessed using hazard ratios (HR) and 95% confidence intervals (CIs) from Cox proportional hazards models, controlling for body mass index and other covariates.ResultsThe highest quintile of flavonol intake was associated with a later age at menarche, compared with the lowest quintile (adjusted HR: 0.80, 95% CI: (0.66–1.00). For lignans, there was a later age in overweight girls (HR: 0.56, 95% CI=0.40–0.80).ConclusionThese dietary bioactives may reflect a healthy diet, and foods high in phytoestrogens may influence the timing of menarche.

We examined the feasibility of conducting a longitudinal study of diet among diverse populations by comparing rates of response throughout recruitment and retention phases by demographic and other characteristics.

IMPORTANCE: There are long-standing interests in the potential benefits of vitamin D for preventing breast cancer recurrence and mortality, yet data from prospective cohort studies are limited. OBJECTIVE: To investigate a serum biomarker of vitamin D status, 25-hydroxyvitamin D (25OHD) measured at the time of breast cancer diagnosis, to determine the association with prognosis. DESIGN, SETTING, AND PARTICIPANTS: The Pathways Study is a prospective cohort study of breast cancer survivors established in 2006. Enrollment was completed in 2013; follow-up is ongoing. The cohort was established in Kaiser Permanente Northern California, a large integrated health care delivery system in northern California. Women with a diagnosis of incident invasive breast cancer were typically consented and enrolled within 2 months of diagnosis. The overall enrollment rate was 46% (4505 of 9820). Participants are followed for health outcomes and comorbidities at 12, 24, 48, 72, and 96 months after baseline interview. A case-cohort design was used for efficiency assay of 25OHD, selecting 1666 cohort members with serum samples and ensuring representation in the subcohort of races and clinical subtypes. The data analysis was performed from January 5, 2014, to March 15, 2015. MAIN OUTCOMES AND MEASURES: Primary outcomes are breast cancer recurrence, second primary cancer, and death. RESULTS: Mean (SD) age was 58.7 (12.4) years. Serum 25OHD concentrations were lower in women with advanced-stage tumors, and the lowest in premenopausal women with triple-negative cancer. Levels were also inversely associated with hazards of disease progression and death. Compared with the lowest tertile, women with the highest tertile of 25OHD levels had superior overall survival (OS). This association remained after adjustment for clinical prognostic factors (hazard ratio [HR], 0.72; 95% CI, 0.54-0.98). Among premenopausal women, the association with OS was stronger, and there were also associations with breast cancer–specific survival and invasive disease–free survival (OS: HR, 0.45; 95% CI, 0.21-0.96; breast cancer–specific survival: HR, 0.37; 95% CI, 0.15-0.93; invasive disease–free survival: HR, 0.58; 95% CI, 0.34-1.01; all after full adjustment). CONCLUSIONS AND RELEVANCE: Serum 25OHD levels were independently associated with breast cancer prognostic characteristics and patient prognosis, most prominently among premenopausal women. Our findings from a large, well-characterized prospective cohort provide compelling observational evidence on associations of vitamin D with lower risk of breast cancer morbidity and mortality.

High recurrence and progression rates are major clinical challenges for non–muscle-invasive bladder cancer (NMIBC). Dietary isothiocyanates (ITCs), phytochemicals primarily from cruciferous vegetables (CV), show strong anticancer activities in preclinical BC models, yet their effect on NMIBC prognosis remains unknown.

IMPORTANCE: Not all women initiate clinically indicated breast cancer adjuvant treatment. It is important for clinicians to identify women at risk for noninitiation. OBJECTIVE: To determine whether complementary and alternative medicine (CAM) use is associated with decreased breast cancer chemotherapy initiation. DESIGN, SETTING, AND PARTICIPANTS: In this multisite prospective cohort study (the Breast Cancer Quality of Care [BQUAL] study) designed to examine predictors of breast cancer treatment initiation and adherence, 685 women younger than 70 years with nonmetastatic invasive breast cancer were recruited from Columbia University Medical Center, Kaiser Permanente Northern California, and Henry Ford Health System and enrolled between May 2006 and July 31, 2010. Overall, 306 patients (45%) were clinically indicated to receive chemotherapy per National Comprehensive Cancer Network guidelines. Participants were followed for up to 12 months. EXPOSURES: Baseline interviews assessed current use of 5 CAM modalities (vitamins and/or minerals, herbs and/or botanicals, other natural products, mind-body self-practice, mind-body practitioner-based practice). CAM use definitions included any use, dietary supplement use, mind-body use, and a CAM index summing the 5 modalities. MAIN OUTCOMES AND MEASURES: Chemotherapy initiation was assessed via self-report up to 12 months after baseline. Multivariable logistic regression models examined a priori hypotheses testing whether CAM use was associated with chemotherapy initiation, adjusting for demographic and clinical covariates, and delineating groups by age and chemotherapy indication. RESULTS: A cohort of 685 women younger than 70 years (mean age, 59 years; median age, 59 years) with nonmetastatic invasive breast cancer were recruited and followed for up to 12 months to examine predictors of breast cancer treatment initiation. Baseline CAM use was reported by 598 women (87%). Chemotherapy was initiated by 272 women (89%) for whom chemotherapy was indicated, compared with 135 women (36%) for whom chemotherapy was discretionary. Among women for whom chemotherapy was indicated, dietary supplement users and women with high CAM index scores were less likely than nonusers to initiate chemotherapy (odds ratio [OR], 0.16; 95% CI, 0.03-0.51; and OR per unit, 0.64; 95% CI, 0.46-0.87, respectively). Use of mind-body practices was not related to chemotherapy initiation (OR, 1.45; 95% CI, 0.57-3.59). There was no association between CAM use and chemotherapy initiation among women for whom chemotherapy was discretionary. CONCLUSIONS AND RELEVANCE: CAM use was high among patients with early-stage breast cancer enrolled in a multisite prospective cohort study. Current dietary supplement use and higher number of CAM modalities used but not mind-body practices were associated with decreased initiation of clinically indicated chemotherapy. Oncologists should consider discussing CAM with their patients during the chemotherapy decision-making process.

IMPORTANCE: Heart disease (HD) and cancer are the 2 leading causes of death in the United States. During the first decade of the 21st century, HD mortality declined at a much greater rate than cancer mortality and it appeared that cancer would overtake HD as the leading cause of death. OBJECTIVES: To determine whether changes in national trends had occurred in recent years in mortality rates due to all cardiovascular disease (CVD), HD, stroke, and cancer and to evaluate the gap between mortality rates from HD and cancer. DESIGN, SETTING, AND PARTICIPANTS: The Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research data system was used to determine national trends in age-adjusted mortality rates due to all CVD, HD, stroke, and cancer from January 1, 2000, to December 31, 2011, and January 1, 2011, to December 31, 2014, overall, by sex, and by race/ethnicity. The present study was conducted from December 30, 2105, to January 18, 2016. MAIN OUTCOMES AND MEASURES: Comparison of annual rates of change and trend in gap between HD and cancer mortality rates. RESULTS: The rate of the decline in all CVD, HD, and stroke mortality decelerated substantially after 2011, and the rate of decline for cancer mortality remained relatively stable. Reported as percentage (95% CI), the annual rates of decline for 2000-2011 were 3.79% (3.61% to 3.97%), 3.69% (3.51% to 3.87%), 4.53% (4.34% to 4.72%), and 1.49% (1.37% to 1.60%) for all CVD, HD, stroke, and cancer mortality, respectively; the rates for 2011-2014 were 0.65% (−0.18% to 1.47%), 0.76% (−0.06% to 1.58%), 0.37% (−0.53% to 1.27%), and 1.55% (1.07% to 2.04%), respectively. Deceleration of the decline in all CVD mortality rates occurred in males, females, and all race/ethnicity groups. For example, the annual rates of decline for total CVD mortality for 2000-2011 were 3.69% (3.48% to 3.89%) for males and 3.98% (3.81% to 4.14%) for females; for 2011-2014, the rates were 0.23% (−0.71% to 1.16%) and 1.17% (0.41% to 1.93%), respectively. The gap between HD and cancer mortality persisted. CONCLUSIONS AND RELEVANCE: Deceleration in the decline of all CVD, HD, and stroke mortality rates has occurred since 2011. If this trend continues, strategic goals for lowering the burden of CVD set by the American Heart Association and the Million Hearts Initiative may not be reached.

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IMPORTANCE: Optimal chemotherapy dosing in obese patients remains uncertain, with variation in practice. Dose reduction strategies are often used to avoid chemotoxicity, but recent American Society of Clinical Oncology guidelines recommend full dose. OBJECTIVE: To evaluate the impact of body mass index (BMI) on chemotherapy dosing and of dose reduction on ovarian cancer survival. DESIGN, SETTING, AND PARTICIPANTS: Cohort study in Kaiser Permanente Northern California (KPNC) health care setting of patients with primary invasive epithelial ovarian cancers diagnosed from January 2000 through March 2013. Analyses focused on 806 patients receiving adjuvant first-line therapy of carboplatin and paclitaxel with curative intent. MAIN OUTCOMES AND MEASURES: Overall and ovarian cancer–specific mortality. Deaths were identified through the KPNC Mortality Linkage System, with median follow-up of 52.5 months. Hazard ratios (HRs) and 95% CIs were estimated from proportional hazards regression, accounting for prognostic variables including age at diagnosis, race, stage, grade, histologic type, chemotoxic effects, comorbidities, cancer antigen 125 levels, and BMI at diagnosis. RESULTS: The strongest predictor of dose reduction was a high BMI. Compared with normal-weight women, obese class III women received 38% and 45% lower doses in milligrams per kilogram of body weight of paclitaxel and carboplatin, respectively (P < .001 for each agent). They also received lower relative dose intensity (RDI) for each agent and the combined regimen, calculated as average RDI (ARDI). Mean ARDI was 73.7% for obese class III women and 88.2% for normal-weight women (P < .001). Lower ARDI (<70%) was associated with worse overall (HR, 1.62 [95% CI, 1.10-2.37]) and ovarian cancer–specific survival (HR, 1.69 [95% CI, 1.12-2.55]). Women who were obese at diagnosis appeared to have better survival. In multivariable-adjusted analyses considering joint effects by BMI and ARDI, compared with women with normal weight and no dose reduction, normal-weight women with dose reduction (ARDI < 85%) experienced worse survival (HR, 1.50 [95% CI, 1.02-2.21]). For each BMI category, those with ARDI less than 85% had worse survival than those without dose reduction. The improved survival among obese women was no longer apparent with dose reduction. CONCLUSIONS AND RELEVANCE: Lower RDI was an independent predictor of ovarian cancer mortality. This finding was strongest among normal-weight women but seen at all levels of BMI. Our results suggest that body size should not be a major factor influencing dose reduction decisions in women with ovarian cancer.

The National Cancer Institute (NCI) Food Reporting and Comparison Study (FORCS) compares nutrient and food group estimates obtained from recalls collected through the web-based Automated Self-Administered 24-hour Recall (ASA24) to those from standard interviewer-administered telephone recalls among 1054 adults. Within the ASA24 software, respondents may choose to enter open-ended text to report “unfound food” and “other, specify.” Respondents use the“unfound food” field to report a food or drink they cannot find; the ASA24 system then asks a series of general questions to better identify the food. Respondents use the “other, specify” field to provide food details, such as brand name or cooking method, that differ from the responses offered by ASA24. When respondents use these two open-ended text fields, the system assigns default food codes. Nutritionists reviewed these codes and assigned new codes when appropriate. Nutrient and My Pyramid Equivalent (MPE) values from default food codes (unedited) andthe researcher assigned food codes (edited)were compared. Of the 716 food codes evaluated, changes were made to 248 foods (1.5% of total foods reported) which affected 194 (19.1%) of all recalls and required over 60hours of specialized staff time. Although 43% of the 1013 completed recalls included at least one of the two text field responses, the ASA24 systemassigned acceptable default food codes 68% of the time.Editing did not significantly affect the means and ranking for most nutrients and food group MPE values; correlation coefficients for energy and macronutrient values before and after editing were 0.95 or higher, suggesting that this editingmaynot be necessary for most large studies using ASA24.

The incidence of and risk factors for severe clinical outcomes with the Omicron (B.1.1.529) SARS-CoV-2 variant have not been well-defined.

Dietary assessment has long been known to be challenged by measurement error. A substantial amount of literature on methods for determining the effects of error on causal inference has accumulated over the past decades. These methods have unrealized potential for improving the validity of data collected for research studies and national nutritional surveillance, primarily through the NHANES. Recently, the validity of dietary data has been called into question. Arguments against using dietary data to assess diet–health relations or to inform the nutrition policy debate are subject to flaws that fall into 2 broad areas: 1) ignorance or misunderstanding of methodologic issues; and 2) faulty logic in drawing inferences. Nine specific issues are identified in these arguments, indicating insufficient grasp of the methods used for assessing diet and designing nutritional epidemiologic studies. These include a narrow operationalization of validity, failure to properly account for sources of error, and large, unsubstantiated jumps to policy implications. Recent attacks on the inadequacy of 24-h recall–derived data from the NHANES are uninformative regarding effects on estimating risk of health outcomes and on inferences to inform the diet-related health policy debate. Despite errors, for many purposes and in many contexts, these dietary data have proven to be useful in addressing important research and policy questions. Similarly, structured instruments, such as the food frequency questionnaire, which is the mainstay of epidemiologic literature, can provide useful data when errors are measured and considered in analyses.

OBJECTIVE To determine the incidence of breast cancer–related lymphedema (BCRL) during the early survivorship period as well as demographic, lifestyle, and clinical factors associated with BCRL development. DESIGN The Pathways Study, a prospective cohort study of breast cancer survivors with a mean follow-up time of 20.9 months. SETTING Kaiser Permanente Northern California medical care program. PARTICIPANTS We studied 997 women diagnosed from January 9, 2006, through October 15, 2007, with primary invasive breast cancer and who were at least 21 years of age at diagnosis, had no history of any cancer, and spoke English, Spanish, Cantonese, or Mandarin. MAIN OUTCOME MEASURE Clinical indication for BCRL as determined from outpatient or hospitalization diagnostic codes, outpatient procedural codes, and durable medical equipment orders. RESULTS A clinical indication for BCRL was found in 133 women (13.3%), with a mean time to diagnosis of 8.3 months (range, 0.7-27.3 months). Being African American (hazard ratio, 1.93; 95% confidence interval, 1.00-3.72) or more educated (P for trend = .03) was associated with an increased risk of BCRL. Removal of at least 1 lymph node (hazard ratio, 1.04; 95% confidence interval, 1.02-1.07) was associated with an increased risk, yet no significant association was observed for type of lymph node surgery. Being obese at breast cancer diagnosis was suggestive of an elevated risk (hazard ratio, 1.43; 95% confidence interval, 0.88-2.31). CONCLUSIONS In a large cohort study, BCRL occurs among a substantial proportion of early breast cancer survivors. Our findings agree with those of previous studies on the increased risk of BCRL with removal of lymph nodes and being obese, but they point to a differential risk according to race or ethnicity.Arch Surg. 2010;145(11):1055-1063--

Abstract Fruit, vegetables, vitamin C, and folate during pregnancy have been suggested as protective factors for medulloblastoma/primitive neuroectodermal tumor (PNET), a common brain tumor in children. The authors sought to replicate these findings and investigate other aspects of diet. Mothers of 315 cases under age six at diagnosis and 315 controls were interviewed about their pregnancy diet. The authors observed modest, inverse associations for fruits/juices (odds ratio (OR) for highest compared to lowest category = 0.6, 95% confidence interval (CI): 0.3, 1.1) and vitamin C (OR = 0.6, 95% CI: 0.4, 1.1). In contrast to the previous study, folate and vegetables showed no association. As hypothesized, cured meats were not associated with medulloblastoma/PNET, in contrast to other childhood brain tumors. An inverse association with nonfresh peaches and similar fruits (OR = 0.5, 95% CI: 0.3, 0.8) and a positive association with nonchocolate candy (OR = 1.7, 95% CI: 1.0, 3.0) replicated previous findings. French fries (OR = 2.4, 95% CI: 1.2, 4.9) and chili peppers (OR = 1.8, 95% CI: 1.0, 3.0) were associated with medulloblastoma/PNET. The results suggest that some aspects of diet are worthy of further research.

More than 20 studies have investigated the relation between meat and dairy food consumption and breast cancer risk with conflicting results. Our objective was to evaluate the risk of breast cancer associated with meat and dairy food consumption and to assess whether non-dietary risk factors modify the relation.

Low B-vitamin intake may increase risk of breast cancer through decreased DNA repair capacity. Alcohol intake increases risk for breast cancer, with evidence from prospective studies of an interaction between alcohol and folate. We explored dietary intake of folate and other B vitamins with risk of breast cancer in a cohort study of 34,387 postmenopausal women. To measure diet, we mailed a food frequency questionnaire; we estimated nutrient intakes and categorized them into four levels <10th, 11th–30th, 31st–50th, and >50th percentiles. Through 12 years of follow-up, we identified 1,586 cases of breast cancer in the cohort at risk. We estimated relative risks (RRs) and 95 confidence intervals (CIs) through Cox regression models adjusted for age, energy, and other risk factors. Women in the lowest 10th percentile of folate intake from diet alone were at modestly increased risk of breast cancer relative to those above the 50th percentile RR 1.21 (95 CI 0.91–1.61). We examined the joint association of folate intake and alcohol use on risk of breast cancer, with the reference group defined as women with high folate (>50th percentile) and no alcohol use. The RRs of breast cancer associated with low dietary folate intake were 1.08 (95 CI 0.78–1.49) among nondrinkers, 1.33 (95 CI 0.86–2.05) among drinkers of ≤4 gm per day, and 1.59 (95 CI 1.05–2.41) among drinkers of >4 gm per day. These results suggest that the risks of postmenopausal breast cancer may be increased among women with low intakes of folate if they consume alcohol-containing beverages.

Recently, there has been interest in whether intakes of specific types of fat are associated with breast cancer risk independently of other types of fat, but results have been inconsistent. We identified 8 prospective studies that met predefined criteria and analyzed their primary data using a standardized approach. Holding total energy intake constant, we calculated relative risks for increments of 5% of energy for each type of fat compared with an equivalent amount of energy from carbohydrates or from other types of fat. We combined study-specific relative risks using a random effects model. In the pooled database, 7,329 incident invasive breast cancer cases occurred among 351,821 women. The pooled relative risks (95% confidence intervals [CI]) for an increment of 5% of energy were 1.09 (1.00–1.19) for saturated, 0.93 (0.84–1.03) for monounsaturated and 1.05 (0.96–1.16) for polyunsaturated fat compared with equivalent energy intake from carbohydrates. For a 5% of energy increment, the relative risks were 1.18 (95% CI 0.99–1.42) for substituting saturated for monounsaturated fat, 0.98 (95% CI 0.85–1.12) for substituting saturated for polyunsaturated fat and 0.87 (95% CI 0.73–1.02) for substituting monounsaturated for polyunsaturated fat. No associations were observed for animal or vegetable fat intakes. These associations were not modified by menopausal status. These data are suggestive of only a weak positive association with substitution of saturated fat for carbohydrate consumption; none of the other types of fat examined was significantly associated with breast cancer risk relative to an equivalent reduction in carbohydrate consumption. © 2001 Wiley-Liss, Inc.

The incidence of breast cancer among women in Shanghai, a traditionally low-risk population, has increased substantially over the past 20 years. To evaluate the association of menstrual and reproductive factors with breast cancer risk and the influence of these factors on the temporal trend of breast cancer incidence, we analyzed data from the Shanghai Breast Cancer Study, a population-based case-control study of breast cancer recently completed among Chinese women in urban Shanghai. In-person interviews were completed for 1,459 women newly diagnosed with breast cancer between ages 25 and 64 and for 1,556 controls frequency-matched to cases by age. Unconditional logistic regression was employed to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) related to menstrual and reproductive factors. Earlier menarcheal age, nulliparity, and later age at first live birth were associated with increased risk of breast cancer among both pre- and post-menopausal women, while never having breast-fed and later age at menopause were associated with elevated risk only among post-menopausal women. Among controls, 32% of younger women (≤40 years) and 24% of older women (>40 years) reported starting menarche at age of 13 or younger, and this factor contributed to 44% of cases diagnosed among younger women and 26% to 28% of cases in older women. Older age at first live birth or at menopause explained a considerable portion of cases diagnosed in older, but not younger, women. Our study suggests that the changes in menstrual and reproductive patterns among women in Shanghai have contributed to the recent increase in breast cancer incidence, particularly among younger women. Int. J. Cancer 87:295–300, 2000. © 2000 Wiley-Liss, Inc.

Background:Inconsistencies in epidemiologic findings relating grain fiber to chronic disease may be explained by differentiating nutrient-rich fiber derived from whole grain vs.nutrient-poor fiber derived from refined grain.Objective:Given that phytochemicals are most varied and abundant in the outer layers of grains, we tested the hypothesis that whole grain fiber consumption is associated with a reduced mortality risk in comparison to a similar amount of refined grain fiber.Design:11040 postmenopausal women enrolled in the Iowa Women’s Health Study, matched on total grain fiber intake, but differing in the proportion of fiber consumed from whole vs.refined grain, were followed from baseline in 1986 through 31 December, 1997, during which time 1341 deaths occurred in 124,823 observed woman-years.Results:After multivariate adjustment in proportional hazards regression, women who consumed on average 1.9 g refined grain fiber/2000 kcal and 4.7 g whole grain fiber/2000 kcal had a 17% lower mortality rate (RR=0.83, 95% CI=0.73–0.94) than women who consumed predominantly refined grain fiber: 4.5 g/2000 kcal, but only 1.3 g whole grain fiber/2000 kcal.Conclusion:Inferences from studies that have reported associations between grain fiber intake and morbidity or mortality may be limited by not differentiating fiber sources. Future studies should distinguish fiber from whole vs.refined grains. Public health policy should differentiate whole grains from refined, and recommend increased consumption of the former.